1. Field of the Invention
Preferred aspects of the present invention relate to multistep filtrations wherein successive filtrations remove filtrates of various specifications. Preferred embodiments of the present invention are particularly useful to regenerate fluid lost during blood dialysis.
2. Description of the Related Art
Traditionally, dialysis is the maintenance therapy used to treat kidney disease. There are two common approaches. One is peritoneal dialysis, wherein the process is done internally to the patient, in the patient's pericardium. Peritoneal dialysis uses the patient's abdominal lining as a blood filter. The abdominal cavity is filled with dialysate, thereby creating a concentration gradient between the bloodstream and the dialysate. Toxins diffuse from the patient's blood stream into the dialysate, which must be exchanged periodically with fresh dialysate.
The second approach is by filtration dialysis. Filtration dialysis encompasses two main filtration techniques: hemodialysis and hemofiltration. Both operate extracorporeally by removing the patient's blood, treating the blood to remove toxins, and returning the processed blood to the patient. Yet, each process functions by a different physical separation technique.
Hemodialysis effects removal of toxins from blood by diffusion. The patient's blood flows past one side of a membrane while dialysate flows past the other side. The membrane selectively allows for the flux of small molecules. Due to the concentration gradient between the blood and the dialysate, small molecule toxins diffuse into the dialysate. At the same time, nutrients, such as electrolytes and other chemicals, present in the dialysate diffuse into the blood. The processed blood is then returned to the patient.
Hemofiltration effects removal of toxins from blood by convection. The patient's blood is passed through a filter that is permeable to plasma water and, generally, molecules smaller than 20,000 Daltons. The resulting plasma water filtrate, called “blood-waste,” contains water, the toxic blood components, and “small desirable molecules,” including small molecule nutrients and electrolytes. Since the processed blood lacks vital components lost through filtration, and since its volume is substantially reduced, a replacement fluid must be added to the processed blood before its reintroduction to the patient. Depending on the hemofiltration needs, the replacement fluid can be added pre- or post-hemofiltration.
In addition to these two blood purification techniques, methods combining hemodialysis and hemofiltration, known as hemodiafiltration, have been used. Hemodiafiltration effects removal of toxins from blood by both diffusion and convection. As in hemofiltration, blood volume and nutrients/electrolytes must be replaced with replacement fluid in hemodiafiltration procedures.
Generally, replacement fluid is engineered to mimic healthy plasma water with respect to pH, electrolyte and nutrient concentration. However, the replacement fluid may also be adjusted to correct for abnormalities in the individual patient. Biologically compatible buffers, such as citrate, lactate, acetate and bicarbonate, often serve as the base for replacement fluids. The buffers may then be supplemented with electrolytes, such as chloride, sodium, calcium, magnesium, potassium, and phosphate, and nutrients, such as glucose and dextrose, as required by the patient.
Disadvantages of these blood processing methods include the difficulties and costs associated with the production of a large amount of replacement fluid that is free of contaminants harmful to the patient. In addition, hemodialysis, hemofiltration and hemodiafiltration create a substantial amount of medical waste that is costly to dispose of. Consequently, there exists a need to recycle the waste from these systems to generate bio-compatible, low cost replacement fluid or dialysate. Thereby, the need for the production of large volumes of foreign dialysate or replacement fluid may be eliminated. Filtration of the patient's blood-waste generated during blood dialysis meets these needs.
Another problem faced by those using well-known methods of blood dialysis is filter clogging, described as “concentration polarization.” As a result of the selective permeability properties of a filter, filtered material that cannot pass through the filter often becomes concentrated on the surface of the filter. This phenomenon is clearly illustrated by the case of a “dead-end” filter, such as a coffee filter. During the course of the filtration process, the filtered material (coffee grounds) building up on the filter creates flow resistance to the filtrate, the fluid (coffee), which can pass through the filter. Consequently, filtrate flux is reduced, and filtration performance diminishes.
Various solutions to the problem of concentration polarization have been suggested. These include: increasing the fluid velocity and/or pressure (see e.g., Merin et al., (1980) J. Food Proc. Pres. 4(3):183-198); creating turbulence in the feed channels (Blatt et al., Membrane Science and Technology, Plenum Press, New York, 1970, pp. 47-97); pulsing the feed flow over the filter (Kennedy et al., (1974) Chem. Eng. Sci. 29:1927-1931); designing flow paths to create tangential flow and/or Dean vortices (Chung et al., (1993) J. Memb. Sci. 81:151-162); and using rotating filtration to create Taylor vortices (see e.g., Lee and Lueptow (2001) J. Memb. Sci. 192:129-143 and U.S. Pat. Nos. 5,194,145, 4,675,106, 4,753,729, 4,816,151, 5,034,135, 4,740,331, 4,670,176, and 5,738,792, all of which are incorporated herein in their entirety by reference thereto). In U.S. Pat. No. 5,034,135, Fischel discloses creating Taylor vorticity to facilitate blood fractionation. Fischel also describes variations in the width of the gap between a rotary spinner and a cylindrical housing, but does not teach variation in this width about a circumferential cross-section.
Taylor vortices are induced in the gap between coaxially arranged cylindrical members when the inner member is rotated relative to the outer member. Taylor-Couette filtration devices generate strong vorticity as a result of centrifugal flow instability (“Taylor instability”), which serves to mix the filtered material concentrated along the filter back into the fluid to be processed. Typically, a cylindrical filter is rotated within a stationary outer housing. It has been observed that membrane fouling due to concentration polarization is very slow compared to dead-end or tangential filtration. Indeed, filtration performance may be improved by approximately one hundred fold.
The use of Taylor vortices in rotating filtration devices has been applied to the separation of plasma from whole blood (See, e.g., U.S. Pat. No. 5,034,135). For this application, the separator had to be inexpensive and disposable for one-time patient use. Further, these separators only had to operate for relatively short periods of time (about 45 minutes). Moreover, the separator was sized to accept the flow rate of blood that could reliably be collected from a donor (about 200 ml/minute). This technology provided a significant improvement to the blood processing industry. The advantages and improved filtration performance seen with rotating filtration systems (Taylor vortices) have not been explored in other areas of commercial fluid separation—including kidney dialysis
Consequently, an improved blood dialysis system may be configured to significantly reduce the artificial replacement fluids necessary. In addition, this improved blood dialysis system may produce Taylor vortices to alleviate the problem of concentration polarization so prevalent with known methods of filtration.